The ongoing objectives of this project were to develop predictive hypotheses about chemical-induced immunotoxicity. This was achieved with a knowledge of the distribution and metabolism of a compound in conjunction with an understanding of the molecular biology inherent in in vitro assays of immune cell function. Three immunoregulatory circuit models were developed to analyze mechanisms of chemical/immunological interaction. The models included: 1) lectin-induced lymphocyte agglutination (an early event of lymphocyte activation) in conjunction with blastogenesis (a late event); 2) lymphokine-induced macrophage activation (agglutination, cytostasis of growing tumor cells); and 3) lymphocyte-mediated growth inhibition (an effector cell function). This approach identified chemical metabolites with "specific" effects on various components of host defense (ip). Work has been completed with 17-Beta estradiol and four of its major metabolites including 2-OH estrone (2-OH E), 2-OCH3 estrone (2-OCH3 E), estrone (E) and 16Alpha-OH estrone (16Alpha-OH E). Although classical cytosolic receptor binding activity has been demonstrated in lymphoid tissue for estrogens, this work suggested that biological response of target cell populations, in many instances, may be more directly associated with nonspecific membrane effects of these compounds. In particular, an important role for catechol estrogen metabolites was suggested. The models may now be applied to other chemical classes.